Pan Jun-Ru, Wang Chen, Yu Qi-Lin, Zhang Shu, Li Bin, Hu Jun
Department of Ophthalmology, Huazhong University of Science and Technology, Wuhan, 430030, China.
The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2014 Jun;34(3):408-414. doi: 10.1007/s11596-014-1292-2. Epub 2014 Jun 18.
The role of methyl-CpG binding domain protein 2 (MBD2) in an ApoE-deficient mouse model of age-related macular degeneration (AMD) was investigated. Eight-week-old Mbd2/ApoE double deficient (Mbd2(-/-) ApoE(-/-)) mice (n=12, 24 eyes, experimental group) and MBD2 (wt) ApoE(-/-) mice (n=12, 24 eyes, control group) were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch's membrane (BM) of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 (ICAM-1) immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group (P>0.05). Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium (RPE) were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group (P<0.05). Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.
研究了甲基化CpG结合域蛋白2（MBD2）在载脂蛋白E缺陷型年龄相关性黄斑变性（AMD）小鼠模型中的作用。将8周龄的Mbd2/ApoE双缺陷（Mbd2(-/-)ApoE(-/-)）小鼠（n = 12，24只眼，实验组）和MBD2（野生型）ApoE(-/-)小鼠（n = 12，24只眼，对照组）用西式饮食喂养4个月。处死小鼠，分析总血清胆固醇水平，并取出眼睛的布鲁赫膜（BM），通过透射电子显微镜进行超微结构观察。此外，通过荧光显微镜评估两组眼睛切片中细胞间黏附分子1（ICAM-1）的免疫反应性，以进一步了解MBD2的功能机制。对照组和实验组的总血清胆固醇水平无显著差异（P>0.05）。透射电子显微镜显示，两组均可见AMD样病变、BM上积聚的各种空泡、明显的外层胶原层沉积物以及视网膜色素上皮（RPE）的基底褶皱扩张，与实验组相比，对照组的BM明显增厚（P<0.05）。荧光显微镜照片显示，对照组脉络膜中ICAM-1的表达高于实验组。我们得出结论，MBD2基因敲除可能导致BM上更多沉积物的积累，并通过触发脉络膜中的内皮细胞活化和炎症反应、改善微循环以及减少脂质沉积来影响AMD的发病机制，从而抑制AMD样病变的发展。我们的研究有助于为AMD的临床治疗提供一种新的治疗方法。
